A Few Questions

amythol · November 2007

I just read a new study which indicated that LCIS may be more of an indication for early stage breast cancer than an indication of risk. I wanted to ask if anyone else on this LCIS page does frequent research on LCIS to get the most current information. If so, what sites are helpful and is there anything new that you have learned?

Also, when I had my prophylactic bilateral mastectomies, I was told that my surgeons would not be able to get every breast cell and there was a very slim chance I could develop breast cancer in the remaining breast cells. My question is, why is radiation therapy not used to try to minimize stray breast cells following PBMs?

leaf · November 2007

I have not learned anything new.

The 'biggest' database (the SEER database) of LCIS and nothing worse patients was the 1988-2001, had about 4500 patients, and in that time period they did not follow such relevant factors as family history, hormone use. I think mastectomy patients, whether unilateral or bilateral, were excluded.

There is not *one* new study that suggests in some cases LCIS may, in some number of circumstances, be a precursor for bc, there are *several*, from different lines of evidence.

Since there are so very few cases of LCIS (without anything worse), there are no web sites specific to LCIS (that I know of), only papers / research.

Thi largest database of studies (that I know of) is Pubmed. http://www.ncbi.nlm.nih.gov/sites/entrez?db=PubMed . Your search results can be *VERY* dependent on your exact search terms. But this site usually only provides abstracts of papers, not the original papers themselves. Sometimes they do: check out the icon next to the reference.

Sometimes, after a big Google search, I have been able to find the complete original paper, but it often does not let me access the paper again.

This was a 2006 survey of almost all (?~95%) of the DCIS and LCIS (and nothing worse) cases (ie using the SEER database) in the US from 1988-2001. There were only about 4500 cases of LCIS in the SEER database during this 13 year period.
CONCLUSIONS: Screening young DCIS patients more frequently and improving the follow-up care of blacks and Hispanic whites with DCIS may reduce their risk of advanced-stage breast cancer. In addition, LCIS may be a precursor rather than just an ambiguous risk factor for invasive breast cancer, and, therefore, localized treatment for LCIS may be warranted. http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=16604564&ordinalpos=2&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

Note: I would not be surprised if the 'codename' for 'local treatment' may be local excision, which I think is commonly done after LCIS is found on core biopsy. However, I do not know this for sure.

There are also other papers that suggest LCIS can SOMETIMES be a precursor - based on chromosome studies, such as

Out of a consecutive series of 88 LCIS, nine patients developed IBC (5 ILC and 4 invasive ductal carcinomas) between 2 and 10 years after initial biopsy. For each case, mitochondrial DNA heteroplasmy was analyzed in normal mammary gland epithelia, LCIS and IBC by PCR, direct DNA sequencing and phylogenetic tree clustering. Two cases of LCIS and ILC showed identical patterns of heteroplasmy. In one further case, additional mtDNA mutations were present in the ILC following LCIS. The remaining two cases of ILC and all 4 IDC were clonally unrelated to the previously diagnosed LCIS. While the overall risk for the development of invasive breast cancer following LCIS is relatively low and the majority of cases are clonally unrelated, our data clearly show that some LCIS eventually do progress to ILC. Thus, LCIS represents both an indicator lesion for an increased risk of subsequent invasive breast cancer and in some cases a precursor of ILC. http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=17380381&ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

Over the decades, there has been a LOT of controversy about LCIS. Up until about 1990, I think most LCIS was treated by bilat mast. This went out of favor when it was found that early invasive breast cancer could often be treated by lumpectomy + rads.

Thus, lobular neoplasia is a risk factor for invasive breast cancer and may be a precursor lesion in unusual circumstances. The management of ALH and LCIS depends on the setting in which they are encountered. When ALH and LCIS are diagnosed after core needle breast biopsy, wire localization for surgical excision is required for definitive diagnosis because rates of histologic underestimation approach those of atypical ductal hyperplasia (ADH). When diagnosed on surgical biopsy, ALH and LCIS generally do not require further intervention, even when present at a surgical margin. However, bilateral breast cancer risk must be considered, especially when patients have a family history of breast cancer. In selected situations, bilateral prophylactic mastectomy with or without reconstruction may be considered when atypical hyperplasia or LCIS is diagnosed. Although this reduces risk for developing subsequent breast carcinoma by 90%, patients selected for prophylactic mastectomy represent a small subgroup of lobular neoplasia patients and generally have other risk factors, such as strong family history or evidence of genetic predisposition. http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=16687097&ordinalpos=3&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

For example, this 1994 paper thinks LCIS should be treated with observation alone.
CONCLUSIONS: Four of 51 women treated with observation alone after diagnosis of LCIS developed breast cancer. All were detected by screening at an early stage. LCIS appeared to be an incidental finding on biopsy of mammographic abnormalities. The policy of observation alone for the finding of LCIS spares women mastectomy. Furthermore, cancers that develop in follow-up are likely to be detected at an early stage and be amenable to curative therapy. Observation alone is appropriate treatment for women with LCIS. http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=7834439&ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstractPlus

I think they have not been ANYWHERE as aggressive about LCIS treatment as DCIS. I think that is because the DEATH rate from LCIS (if it progresses to invasive bc)is low. In this 5 year study of 180 LCIS patients,

Only 2 patients in the cohort (1.1%) succumbed to breast carcinoma; 1 patient had a prior invasive IBTR, and the other patient had an invasive CBTR....CONCLUSIONS: LCIS is a more indolent form of in situ breast carcinoma than DCIS, with which it shares other features of its natural history, particularly very low mortality rates. There is no compelling reason to surgically treat LCIS other than conservatively. The values of other adjuvant modalities in the management of LCIS are discussed. The authors acknowledge that their findings are based on relatively few events and, even at 12 years, may be regarded as "preliminary". Nonetheless, their findings may reflect the true biologic nature of LCIS. Copyright 2003 American Cancer Society. http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=14716756&ordinalpos=4&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

In this earlier study of LCIS from the SEER database 1973-1998 (when PBMs were much more common), RESULTS: The incidence of IBC increased over time from diagnosis of LCIS, with 7.1% +/- 0.5% incidence of IBC at 10 years. IBCs detected after partial mastectomy occurred in either breast (46% ipsilateral and 54% contralateral); however, after mastectomy, most IBCs were contralateral (94.7%). http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=16110014&ordinalpos=11&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

I think some of the hesitations people have of using radiation for LCIS include:
a) LCIS is usually multifocal, and often bilateral. Does that mean you'd want bilateral radiation?
b) If you gave a person bilateral radiation for LCIS, then *if* they later got DCIS or worse, I don't think you would have the option of using radiation again. I thought (and please correct me if I am wrong) that you can use radiation once.

But note, almost all of the studies I've seen give numbers where the *majority* of women with LCIS and nothing worse, at least if they do not have a bad family history, do *NOT* get bc during their lifetime.

That said, am I terrified of getting breast cancer because of my LCIS (and weak family history)? You bet I am. Women vary a lot. Some of us opt to keep their breasts and go on the 'roller coaster ride' (ie close screening), or take tamoxifen/AI and the 'roller coaster' ride, or some of is choose PBMs.
I don't handle the screening well at ALL.

We are all different, and I think YOU should have total control over YOUR choices. It is YOUR body and YOUR life.

I will post more later if I can, but I have several other projects I need to do.

Anonymous · November 2007

amy----I haven't read or heard of any other new studies on LCIS (other than the ones Leaf already mentioned)--it seems like the research and studies are sorely lacking when it comes to LCIS---we need more to figure out all these issues!!!! As far as the radiation goes, my surgeon said radiation is not given for LCIS since it is non-invasive, but even if it was given, they wouldn't know where exactly to radiate since LCIS is so often multicentric, multifocal, and bilateral, so in theory you'd have to radiate both breasts completely and they don't do that for many medical reasons. One of my fears is that some day in the future, they are going to decide that perhaps they should've been treating LCIS more like DCIS all along due to more opinions/studies coming out about LCIS actually being a precursor of invasive disease rather than just a high risk marker, but that's JMO. The risk of recurrence of invasive bc is drastically reduced after bilat. mastectomies, and I would think your risk would be even smaller, since you didn't have an invasive bc before your BPMs. I go thru times when I feel like I'm doing all I can to prevent an invasive bc (tamox and very close monitoring) and times when I question myself about my choices. I think that's normal, we all do it, but I think you have done all that you can with what they know now about LCIS. Again, I admire your courage. I hope you are recovering well with no more complications.

Anne

Anonymous · November 2007

Amy---just remembered something my surgeon told me when I asked him what percentage of LCIS goes on to become invasive bc? He said they didn't really know, but he would guess it was a small number, "probably 5%". So if BPMs reduced your risk by 90%, your remaining risk would only be 0.5%, and that number could even be even smaller! So I think you can probably feel very confident that your risk is very, very small now that you had your surgery. I just read an article (I don't know how to copy a link, but if you google ingentaconnect, you may see it---"evaluating the extent of lobular neoplasia on the risk of invasive bc") that implied there is more risk of invasive bc with diffuse LCIS than with localized LCIS. Makes sense--the more areas of LCIS that there are, the more chances for invasive bc to be lurking in there along with it. Again, I hope you're doing well.

Anne

nash · November 2007

Thought I'd chime in here with a ponderance on rads for LCIS. My ILC tumor was surrounded by LCIS, which is still in my breast, as I only had a lumpectomy. However, the LCIS was growing into the chest wall. The surgeon thinks she got a clean margin, but there was some debate as to whether the inked margin had run or if the margin was actually dirty.

In the end, the surgeon decided the margin was clean of LCIS. But the reason it's an issue now is because I'm almost done with chemo and the onc is starting to talk about rads. I obviously need rads b/c of the ILC lumpectomy site, but she said the rads onc will have to decide if I need a boost to the chest wall b/c of the LCIS growing into it. Then she says, "Of course, we don't know if LCIS responds to radiation." Terrific. So I have to decided if I want a radiation boost that could potentially do even more heart and lung damage than I'm already going to be getting, or if I want to take my chances. Since my ILC seems to have arisen directly from my LCIS (both are of the pleomorphic variety), the surgeon already said that if I have a local recurrence, it will probably be in the chest wall.

Don't know exactly what my point is other than to moan about how hard it is to make treatment decisions when the docs themselves don't really know what's going on. Undecided

leaf · November 2007

I don't think there is very much literature at all on pleomorphic LCIS, let alone your situation.

But there is this paper on radiation + LCIS and nothing worse.

Eur J Cancer. 2005 Feb;41(3):380-5. Links

Breast-conserving surgery and radiotherapy: a possible treatment for lobular carcinoma in situ?

Cutuli B, de Lafontan B, Quetin P, Mery E.

Department of Radiation Oncology, Polyclinique de Courlancy, 38 rue de Courlancy, 51100 Reims, France. b.cutuli@wanadoo.fr

Lobular carcinoma in situ (LCIS) is generally treated by conservative surgery alone and less often by mastectomy. We report our experience using conservative surgery and whole breast irradiation (WBI) for the treatment of patients with LCIS. From 1980 to 1992, 25 women with a median age of 54 years underwent lumpectomy (20) or quadrantectomy (5) and WBI (median dose: 52 Gy) for treatment of their LCIS. Five cases had palpable lesions, 19 were found by mammography alone and one case was found due to nipple discharge. Twelve women received tamoxifen at 20 mg/day for 2 years. With a median follow-up of 153 months (range 58-240), only one local recurrence was observed. The global rate of bilateral carcinoma was 17.6% (two synchronous and one metachronous). Until now, no case of LCIS treated by lumpectomy and radiation therapy has been reported in detail in the literature. After biopsy alone for LCIS, a subsequent infiltrating carcinoma occurs in approximately 15% of cases. Thus, classical radiosurgical therapy should represent an interesting alternative both for limited surgery alone and mastectomy, both of which have been proposed as sole treatments for LCIS.

PMID: 15691636 [PubMed - indexed for MEDLINE]

*******

I did find several papers when LCIS was found WITH invasive, but, of course, they don't agree.

Cancer. 2000 Mar 1;88(5):1072-7. Links

The relation between the presence and extent of lobular carcinoma in situ and the risk of local recurrence for patients with infiltrating carcinoma of the breast treated with conservative surgery and radiation therapy.

Abner AL, Connolly JL, Recht A, Bornstein B, Nixon A, Hetelekidis S, Silver B, Harris JR, Schnitt SJ.

Joint Center for Radiation Therapy, Harvard Medical School, Boston, MA 02215, USA.

BACKGROUND: When found in an otherwise benign biopsy, lobular carcinoma in situ (LCIS) has been associated with an increased risk of development of a subsequent invasive breast carcinoma. However, the association between LCIS and the risk of subsequent local recurrence in patients with infiltrating carcinoma treated with conservative surgery and radiation therapy has received relatively little attention. METHODS: Between 1968 and 1986, 1625 patients with clinical Stage I-II invasive breast carcinoma were treated at the Joint Center for Radiation Therapy at Harvard Medical School with breast-conserving surgery (CS) and radiation therapy (RT) to a total dose to the primary site of > or =60 grays. Analysis was limited to 1181 patients with infiltrating ductal carcinoma, infiltrating lobular carcinoma, or infiltrating carcinoma with mixed ductal and lobular features who, on review of their histologic slides, had sufficient normal tissue adjacent to the tumor to evaluate for the presence of LCIS and also had a minimum potential follow-up time of 8 years. The median follow-up time was 161 months. RESULTS: One hundred thirty-seven patients (12%) had LCIS either within the tumor or in the macroscopically normal adjacent tissue. The 8-year crude risk of recurrence was not significantly increased for patients with LCIS associated with invasive ductal, invasive lobular, or mixed ductal and lobular carcinoma. Among the 119 patients with associated LCIS adjacent to the tumor, the 8-year rate of local recurrence was 13%, compared with 12% for the 1062 patients without associated LCIS. For the 70 patients with moderate or marked LCIS adjacent to the tumor, the 8-year rate of local recurrence was 13%. The extent of LCIS did not affect the risk of recurrence. The risks of contralateral disease and of distant failure were similarly not affected by the presence or extent of LCIS. CONCLUSIONS: Breast-conserving therapy involving limited surgery and radiation therapy is an appropriate method of treating patients with invasive breast carcinoma with or without associated LCIS. Neither the presence nor the extent of LCIS should influence management decisions regarding patients with invasive breast carcinoma. [See editorial counterpoint and reply to counterpoint on pages 978-81 and 982-3, this issue.] Copyright 2000 American Cancer Society.

PMID: 10699897 [PubMed - indexed for MEDLINE]

Cancer. 2006 Jan 1;106(1):28-34. Links

Is lobular carcinoma in situ as a component of breast carcinoma a risk factor for local failure after breast-conserving therapy? Results of a matched pair analysis.

Ben-David MA, Kleer CG, Paramagul C, Griffith KA, Pierce LJ.

Department of Radiation Oncology, Cancer and Geriatrics Center, University of Michigan Medical School, Ann Arbor, Michigan 48109-0010, USA.

BACKGROUND: The goals of the current study were to compare the clinicopathologic presentations of patients with lobular carcinoma in situ (LCIS) as a component of breast carcinoma who were treated with breast conserving surgery (BCS) and radiation therapy (RT) with those of patients without LCIS as part of their primary tumor and to report rates of local control by overall cohort and specifically in patients with positive margins for LCIS and multifocal LCIS. METHODS: Sixty-four patients with Stages 0-II breast carcinoma with LCIS (LCIS-containing tumor group, LCTG) that had received BCS+RT treatment at the University of Michigan between 1989 and 2003 were identified. These patients were matched to 121 patients without LCIS (control group) in a 1:2 ratio. RESULTS: The median follow-up time was 3.9 years (range, 0.3-18.9 yrs). There were no significant differences between the two groups with regard to clinical, pathologic, or treatment-related variables or in mammographic presentation, with the exception of a higher proportion of the LCTG patients who received adjuvant hormonal therapy (P = 0.01). The rates of local control at 5 years were 100% in the LCTG group and 99.1% in the control group (P = 0.86). The presence of LCIS at the margins and the size and presence of multifocal LCIS did not alter the rate of local control. CONCLUSIONS: The extent of LCIS and its presence at the margins did not reduce the excellent rates of local control after BCS+RT. The data suggest that LCIS in the tumor specimen, even when multifocal, should not affect selection of patients for BCS and whole-breast RT. Copyright 2005 American Cancer Society.

PMID: 16329136 [PubMed - indexed for MEDLINE]

Int J Radiat Oncol Biol Phys. 2006 Oct 1;66(2):365-71. Links

The impact of lobular carcinoma in situ in association with invasive breast cancer on the rate of local recurrence in patients with early-stage breast cancer treated with breast-conserving therapy.

Jolly S, Kestin LL, Goldstein NS, Vicini FA.

Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI 48073, USA.

PURPOSE: The significance of lobular carcinoma in situ (LCIS) associated with invasive breast cancer in patients undergoing breast-conserving therapy (BCT) remains controversial. We examined the impact of the presence and extent of LCIS associated with invasive breast cancer on clinical outcome in BCT patients. METHODS AND MATERIALS: From 1980 to 1996, 607 cases of invasive breast cancer were treated with BCT. All slides were reviewed by a single pathologist. Positive margin was defined as presence of invasive carcinoma/ductal carcinoma in situ at the inked margin. Multiple clinical, pathologic, and treatment-related variables were analyzed for their association with ipsilateral breast tumor recurrence (IBTR) and true recurrence/marginal miss (TR/MM). Median follow-up was 8.7 years. RESULTS: Fifty-six patients (9%) had LCIS in association with invasive cancer. On univariate analysis, positive final margin, positive/no reexcision, smaller maximum specimen dimension, and the presence of LCIS predicted for IBTR. The 10-year IBTR rate was 14% for cases with LCIS vs. 7% without LCIS (p=0.04). On multivariate analysis, positive margin (p
PMID: 16965988 [PubMed - indexed for MEDLINE]

These of course do not say they include pleomorphic LCIS or pleomorphic ILC.

Just as you said, its so very hard to make treatment decisions when the docs don't know themselves, let alone what insurance companies feel. The groups they are comparing, even in these papers, are small. As others have said, we deserve better.

nash · November 2007

Thanks for the articles, leaf!

leaf · November 2007

You're welcome, of course, nash!

Anonymous · November 2007

Leaf---Thank you for the articles. I'm wondering if any studies have been done in the USA like the one in France (radiation for LCIS)?

nevaeh · November 2007

Leaf,

You are a wonder and a gift to us all.

Nash, you wrote "how hard it is to make treatment decisions when the docs themselves don't really know what's going on. Undecided " and BOY did I hear you! I feel very alone sometimes, until I come here to this list and find all your caring hearts.

The consensus among all my dr's is LCIS is a precursor and not a precancer. From what I've read this seems to be the "opinion" of the day. I wonder if LCIS was a precusor for impotence "precusor" would be used so lightly and our concerns dismissed so easily.

leaf · November 2007

Nash:There is this 2002 paper is one of the few I’ve found that even mentions PLCIS with invasive pleomorphic lobular. I know this does not give you any guide as what to do, but you may gain some info. I do NOT have complete information; my background in microbiology is poor, but you may like to read.

We reviewed 10 cases of pleomorphic lobular (ductal lobular) carcinoma in situ (PL/DLCIS) of the breast and compared them with 14 cases of pleomorphic lobular carcinoma in situ (PLCIS) found in association with invasive pleomorphic lobular carcinoma. The histologic features; immunohistochemical staining for estrogen receptors (ERs), p53, Ki67, E-cadherin, and gross cystic disease fluid protein-15 (GCDFP-15); and results of fluorescence in situ hybridization for HER-2/neu gene amplification were evaluated in all 24 cases. Histologically, PL/DLCIS cells were similar to those of PLCIS with invasion in that they were discohesive and medium to large in size with moderate to marked nuclear pleomorphism, small to prominent nucleoli, and moderate to abundant eosinophilic or vacuolated cytoplasm. In both groups, central necrosis was present in a small number of cases, and classic LCIS coexisted with the in situ lesion in less than half of the cases; in situ carcinomas were positive for ERs in 23 (100%) of 23 cases, p53 in 6 (25%) of 24 cases, and GCDFP-15 in 14 (74%) of 19 cases. The percentage of Ki67-positive tumor nuclei indicated moderate to high (more than 20%) proliferative activity in 8 (47%) of 17 cases. Immunostaining for E-cadherin was negative in all 24 cases. HER-2/neu gene amplification was observed in 1 (4%) of 23 cases. In cases with associated invasion, PLCIS had cytologic features and immunostaining patterns similar to those of the invasive pleomorphic component. Seven of the 10 patients who had PL/DLCIS without invasion underwent lumpectomy or simple mastectomy. Six of these patients had no evidence of disease in follow-up periods ranging from 4 to 32 months; the seventh patient developed recurrent disease 12 months after undergoing lumpectomy. We conclude that the cytologic features and biomarker expression profile of PL/DLCIS are similar to those of PLCIS with invasion but somewhat different from those of classic LCIS and ductal carcinoma in situ. Long-term follow-up studies are needed to further define the natural history of PL/DLCIS and its optimal management.

Keywords: Breast, Breast cancer, Invasive pleomorphic lobular carcinoma, Lobular carcinoma, Lobular carcinoma in situ, Pleomorphic lobular carcinoma in situ

Pleomorphic LCIS (PLCIS) is a recently recognized variant of LCIS (2, 3, 4, 5). However, all of the PLCIS cases described in the literature have been associated with infiltrating pleomorphic lobular carcinoma (IPLC) at a frequency of approximately 50% of IPLC cases (2, 3, 4). In those reports, PLCIS was described as being cytologically similar to IPLC with a cell population consisting of large, pleomorphic, dyshesive cells with eccentric nuclei and eosinophilic cytoplasm. Although lesions similar to PLCIS but lacking associated invasion have been encountered, the striking cytologic differences between them and classic LCIS and occasional associated necrosis made distinction of these lesions from solid DCIS difficult. Consequently, such lesions have been designated as indeterminate, mixed ductal lobular carcinoma in situ (DLCIS) (1, 6, 7, 8), or "florid" PLCIS (5). To our knowledge, there have been no reports of PLCIS/DLCIS (PL/DLCIS) as an isolated lesion without associated invasive carcinoma, and information about the natural history of PL/DLCIS is lacking. In addition, the clinical and mammographic presentation and biomarker characteristics of PL/DLCIS are not known. http://www.nature.com/modpathol/journal/v15/n10/full/3880650a.html

leaf · November 2007

awb: I cannot find any articles about treating LCIS (with nothing worse) with radiation besides in France. I am not a librarian and do not have complete info. This 1998 paper is from France too. I can’t find anything else, but I am not an expert on this.

1: Oncol Rep. 1998 Nov-Dec;5(6):1531-3.

Links

Lobular carcinoma in situ of the breast: results of a radiosurgical conservative treatment.

Cutuli B, Jaeck D, Renaud R, Rodier JF.

Centre Paul Strauss, 67085 Strasbourg Cedex, France.

From 1980 to 1992, 17 women underwent lumpectomy (13) or quadrantectomy (4) and whole breast irradiation (median dose: 52 Gy) for pure lobular carcinoma in situ (LCIS). Three cases correspond to palpable lesions and 14 were discovered only by mammography. Twelve women also received tamoxifen at 20 mg/day for two years. With a median follow-up of 88 months, no local or regional recurrences have been recorded. The global rate of bilateral carcinoma was 17.6% (2 synchronous and one metachronous). In the literature, only eight other cases of LCIS were treated by lumpectomy and radiation therapy, but without details and data on long-term results. After biopsy alone for LCIS subsequent infiltrating carcinoma occurred in about 15% of the cases. Thus, the classical radiosurgical association should represent an interesting alternative both for biopsy alone and radical surgery until now only proposed to treat LCIS.

PMID: 9769400 [PubMed - indexed for MEDLINE]

leaf · November 2007

neveah:
From what I have read, I cannot find the data from most papers saying that most/all of the breast cancers that LCIS women get are clonally related, though some are. I think the numbers from most of these studies are simply too small to draw conclusions.

(I may be repeating myself with some of these papers.)

In this 1998 paper (the 182 LCIS patients in the NSABP B-17 study) they found some LCIS women got DCIS alone, and again, do not recommend mastectomy for LCIS.

(Note: I find it curious that the 1996 paper recommends the name LCIS,whereas the current NCI website recommends the term lobular neoplasia for LCIS, as stated below.)

The term lobular carcinoma in situ (LCIS) is misleading. This lesion is more appropriately termed lobular neoplasia. Strictly speaking, it is not known to be a premalignant lesion, but rather a marker that identifies women at an increased risk for subsequent development of invasive breast cancer. This risk remains elevated even beyond 2 decades, and most of the subsequent cancers are ductal rather than lobular. LCIS is usually multicentric and is frequently bilateral. In a large prospective series from the National Surgical Adjuvant Breast and Bowel Project with a 5-year follow-up of 182 women with LCIS managed with excisional biopsy alone, only eight women developed ipsilateral breast tumors (four of the tumors were invasive).[1] In addition, three women developed contralateral breast tumors (two of the tumors were invasive).

http://www.cancer.gov/cancertopics/pdq/treatment/breast/HealthProfessional/page6

Cancer. 1996 Oct 1;78(7):1403-16.
Links
Pathologic findings from the National Surgical Adjuvant Breast Project (NSABP) Protocol B-17. Five-year observations concerning lobular carcinoma in situ.
Fisher ER, Costantino J, Fisher B, Palekar AS, Paik SM, Suarez CM, Wolmark N.
Institute of Pathology, Shadyside Hospital, Pittsburgh, Pennsylvania 15232, USA.
BACKGROUND: Extant information reveals inconsistencies concerning the natural history, pathologic features, and treatment of lobular carcinoma in situ (LCIS) of the breast. It is uncertain whether these are related to the methods of study, diagnostic criteria employed, relative paucity of cases, or varying lengths of follow-up. METHODS: The cohort was comprised of 182 women with LCIS who were enrolled in National Surgical Adjuvant Breast Project (NSABP) Protocol B-17 but received no treatment other than lumpectomy. Nineteen pathologic features were assessed and related to ipsilateral breast tumor recurrence (IBTR) and contralateral breast tumor recurrence (CBTR) at a mean time on study of 5 years. RESULTS: Thirteen IBTR and 4 CBTR, including 1 instance of bilateral recurrence, were observed. All IBTR occurred in the same quadrant as the index LCIS. All 4 (2.2%) IBTR that were invasive cancers were of the lobular type, as was 1 of the 2 (1.1%) CBTR that were invasive. The other was a mucinous carcinoma. Three (1.6%) IBTR were pure ductal carcinoma in situ (DCIS) and another was accompanied by LCIS. One instance of CBTR was also comprised of DCIS and LCIS. The remaining five IBTR and one CBTR were LCIS only. The only pathologic parameter found to be significantly predictive for invasive IBTR and DCIS was type 3 and, to a lesser extent, type 2 LCIS. Some heretofore unrecognized or little appreciated pathologic features of LCIS are noted. Ancillary histochemical findings strongly implicate the derivation of LCIS from ductal or secretory cells rather than "new cells" or myoepithelial elements. All examples tested were found to be c-erb B-2 negative, universally diploid with normoproliferative DNA content, and estrogen receptor and progesterone receptor positive. No other events related to the breast were encountered. CONCLUSIONS: The number of events observed in this large cohort of patients with LCIS is markedly less than that noted by others after a comparable period of follow-up. Possible reasons for this dichotomy, including differences in patient characteristics, diagnostic criteria, and status of resection margins, are discussed. Considerations are also offered to support the view that LCIS may exhibit precursor activity as well as represent a risk factor (the term marker is literally inaccurate). In this light, the designation LCIS rather than lobular neoplasia is preferred. These preliminary findings and historical information presented in this study fail to provide any reason to perform mastectomy on patients with LCIS.
PMID: 8839545 [PubMed - indexed for MEDLINE]
****

In this study, 14 out of 24 samples were more related to the LCIS than other ILCs. That means that 10 were *not*.

Cancer. 2004 Jun 15;100(12):2562-72. Links
Clonality of lobular carcinoma in situ and synchronous invasive lobular carcinoma.

Shelley Hwang E, Nyante SJ, Yi Chen Y, Moore D, DeVries S, Korkola JE, Esserman LJ, Waldman FM.
Department of Surgery, University of California-San Francisco, San Francisco, California 94115, USA. shelley.hwang@ucsfmedctr.org
BACKGROUND: Lobular carcinoma in situ (LCIS) of the breast is considered a marker for an increased risk of carcinoma in both breasts. However, the frequent association of LCIS with invasive lobular carcinoma (ILC) suggests a precursor-product relation. The possible genomic relation between synchronous LCIS and ILC was analyzed using the technique of array-based comparative genomic hybridization (CGH). METHODS: Twenty-four samples from the University of California-San Francisco pathology archives that contained synchronous LCIS and ILC were identified. Array CGH was performed using random primer-amplified microdissected DNA. Samples were hybridized onto bacterial artificial chromosome arrays composed of approximately 2400 clones. Patterns of alterations within synchronous LCIS and ILC were compared. RESULTS: A substantial proportion of the genome was altered in samples of both LCIS and ILC. The most frequent alterations were gain of 1q and loss of 16q, both of which usually occurred as whole-arm changes. Smaller regions of gain and loss were seen on other chromosome arms. Fourteen samples of LCIS were related more to their paired samples of ILC than to any other ILC, as demonstrated by a weighted similarity score. CONCLUSIONS: LCIS and ILC are neoplastic lesions that demonstrate a range of genomic alterations. In the current study, the genetic relation between synchronous LCIS and ILC suggested clonality in a majority of the paired specimens. These data were consistent with a progression pathway from LCIS to ILC. The authors conclude that LCIS, which is known to be a marker for an environment that is permissive of neoplasia, may itself represent a precursor to invasive carcinoma. Copyright 2004 American Cancer Society.
PMID: 15197797 [PubMed - indexed for MEDLINE]

This study suggests a precursor role, but doesn't give any statistics.
Genes Chromosomes Cancer. 2006 Nov;45(11):1007-17. Links
Genomic alterations in lobular neoplasia: a microarray comparative genomic hybridization signature for early neoplastic proliferationin the breast.

Mastracci TL, Shadeo A, Colby SM, Tuck AB, O'Malley FP, Bull SB, Lam WL, Andrulis IL.
Fred A. Litwin Centre for Cancer Genetics, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON, Canada.
The identification of genomic alterations occurring in neoplastic lesions provides insight into both lesion occurrence and disease progression. In this study, we used microarray comparative genomic hybridization (CGH) to investigate genetic changes in atypical lobular hyperplasia (ALH) and lobular carcinoma in situ (LCIS), as the presence of these lobular neoplastic lesions is an indicator of risk in the development of invasive breast cancer. DNA was extracted from microdissected archival breast tissue containing ALH or LCIS, lacking adjacent invasive carcinoma, and subjected to whole-genome tiling path microarray-CGH using the submegabase resolution tiling set (SMRT)-array platform. Twelve ALH and 13 LCIS lesions were examined. Copy number alterations were identified using statistical criteria and validated with Real-Time PCR and fluorescence in situ hybridization. From statistical analysis, a greater number of alterations were observed in ALH compared to LCIS. Alterations common to ALH include gain at 2p11.2 and loss at 7p11-p11.1 and 22q11.1. Alterations common to LCIS include gain at 20q13.13 and loss at 19q13.2-q13.31. In both ALH and LCIS, we observed loss of 16q21-q23.1, an altered region previously identified in lobular neoplasia and invasive carcinoma. The validation of select alterations reinforces the genomic signature. This study represents the first whole-genome investigation of lobular neoplastic breast lesions using clinical archival specimens. The identified genomic signature includes copy number alterations not previously identified for lobular neoplasia. This genomic signature, common to ALH and LCIS, suggests a role for the acquisition of novel genomic alterations in the aberrant cellular proliferation that defines lobular neoplasia. (c) 2006 Wiley-Liss, Inc.

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The other line of reasoning, looks at what breast cancers are seen (ie women who got invasive + LCIS)shows that roughly half of the invasive cancers are ductal. In this report, 6 out of 9 cases were clonally *unrelated* to the LCIS. These are *very* small numbers.

1: Breast Cancer Res Treat. 2007 Mar 23; [Epub ahead of print]
Links
Clonality of lobular carcinoma in situ (LCIS) and metachronous invasive breast cancer.
Aulmann S, Penzel R, Longerich T, Funke B, Schirmacher P, Sinn HP.
Department of Pathology, University of Heidelberg, Im Neuenheimer Feld 220, 69120, Heidelberg, Germany, sebastian_aulmann@med.uni-heidelberg.de.
Lobular carcinoma in situ (LCIS) of the breast is generally considered an indicator for a bilaterally increased risk of invasive breast cancer (IBC). However, as recent studies suggested a clonal relationship between a subset of synchronous LCIS and invasive lobular carcinomas (ILC), we aimed to examine a possible precursor role for LCIS and IBC occurring in the same breast at a later time. Out of a consecutive series of 88 LCIS, nine patients developed IBC (5 ILC and 4 invasive ductal carcinomas) between 2 and 10 years after initial biopsy. For each case, mitochondrial DNA heteroplasmy was analyzed in normal mammary gland epithelia, LCIS and IBC by PCR, direct DNA sequencing and phylogenetic tree clustering. Two cases of LCIS and ILC showed identical patterns of heteroplasmy. In one further case, additional mtDNA mutations were present in the ILC following LCIS. The remaining two cases of ILC and all 4 IDC were clonally unrelated to the previously diagnosed LCIS. While the overall risk for the development of invasive breast cancer following LCIS is relatively low and the majority of cases are clonally unrelated, our data clearly show that some LCIS eventually do progress to ILC. Thus, LCIS represents both an indicator lesion for an increased risk of subsequent invasive breast cancer and in some cases a precursor of ILC .PMID: 17380381 [PubMed - as supplied by publisher]

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